Characteristics and determinants of endurance cycle ergometry and six-minute walk distance in patients with COPD

BACKGROUND: Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD). We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients. METHODS: A dataset of 2053 COPD patients (43% female, age: 66.9 ± 9.5 years, FEV(1)% predicted: 48.2 ± 23.2) was analyzed retrospectively. Patients underwent, amongst others, respiratory function evaluation; medical tests and questionnaires, one maximal incremental cycle test where peak work rate was determined and two functional exercise tests: a CET at 75% of peak work rate and 6MWT. A stepwise multiple linear regression was used to assess determinants. RESULTS: On average, patients had impaired exercise tolerance (peak work rate: 56 ± 27% predicted, 6MWT: 69 ± 17% predicted). A total of 2002 patients had CET time of duration (CET-T(end)) less than 20 min while only 51 (2.5%) of the patients achieved 20 min of CET-T(end) . In former patients, the percent of predicted peak work rate achieved differed significantly between men (48 ± 21% predicted) and women (67 ± 31% predicted). In contrast, CET-T(end) was longer in men (286 ± 174 s vs 250 ± 153 s, p < 0.001). Also, six minute walking distance (6MWD) was higher in men compared to women, both in absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m, 72%predicted, p < 0.05). Gender was associated with the CET-T(end) but BMI, FEV(1) and FRC were related to the 6MWD highlighting the different determinants of exercise performance between CET and 6MWT. CONCLUSIONS: CET-T(end) is a valuable outcome of CET as it is related to multiple clinical aspects of disease severity in COPD. Gender difference should temper the interpretation of CET

Treatable traits in the European U-BIOPRED adult asthma cohorts

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Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

European Translational Research Informatics and Knowledge Services (eTRIKS): reducing the effort needed to preserve and explore translational research data

eTRIKS is a public/private partnership funded by the Innovative Medicines Initiative (IMI). Unlike most IMI projects, eTRIKS was specifically created to support research collaborations in their translational research data knowledge management needs. <br>Many aspects of managing and working in research collaborations are complex and challenging. Working with the datasets generated in a research collaboration is no exception. There have to be solutions for where databases will be hosted, how access will be controlled, complying with data protection and privacy regulations, integration of different data types, organizing the analysis process, and preserving your data for future use. Currently many datasets reside in 'silos' and new platforms are developed for each new project making the integration and re-use of existing data assets difficult. <br>The mission of eTRIKS is to Maximize the impact of translational research datasets by providing platforms, services, guidance, and trainings that enable the efficient integration, staging, exploration, preservation, and reuse of translational research data.<br>eTRIKS has supported over 30 research collaborations in the last 4 years. We have established know how in advising and supporting projects. Perhaps more importantly eTRIKS has contributed to the development of the open source tranSMART knowledge management platform. Recently the effort has been focused on developing tools to improve data curation as well as better data visualisations, data exploration, and a catalogue of translational research project databases. In addition eTRIKS has developed a translational research data standards starter pack and has contributed to the developed of a code of practice for medical research data re-use. We are also working to address gaps in awareness about the value of medical research data re-use by engaging patients and other stakeholders using a discussion game to build mutual understanding about differences in perspective. <br>In the presentation use cases and examples of how eTRIKS has supported research collaborations will be shown. Some of the open source tools that support data warehousing and data exploration will also be illustrated. <br>Looking to the future eTRIKS know how and assets will be preserved in an eTRIKS network that will continue to support research collaborations including low or no cost solutions for preserving translational research datasets.<br><br><b>Disclosure</b>: Scott Wagers is the CEO of BioSci Consulting which receives funding the IMI as a partner of eTRIKS. BioSci Consulting also provides services for managing research collaborations and will be organising the efforts of the eTRIKS Network

Age-graded reductions in quadriceps muscle strength and peak aerobic capacity in COPD

BACKGROUND: Reductions in quadriceps strength and peak aerobic capacity (VO2) in patients with chronic obstructive pulmonary disease (COPD) have been studied in relatively small samples over a short period. Moreover, results were not corrected for confounding variables, such as lean muscle mass, gender, and gas transfer capacity of the lungs. OBJECTIVES: To compare quadriceps muscle strength and peak V.O2 in women and men while stratifying for age and gas transfer capacity. We then corrected for lower-limb lean muscle mass to see whether and to what extent the age-graded reduction remained evident. METHODS: Retrospectively, data of 374 women and 593 men with COPD were analyzed: lung function, current drug therapy, quadriceps strength, peak V.O2, lower-limb lean muscle mass, and gas transfer capacity. RESULTS: Quadriceps strength and peak V.O2 were lower in older women and men with a gas transfer capacity of 50% predicted. Yet, counter to our hypothesis, lower-limb lean muscle mass did not show an age-graded reduction and, in turn, could not account for the relationship of age with quadriceps strength and peak V.O2. CONCLUSIONS: It is apparent that there is an age-graded reduction in skeletal muscle function in patients with COPD. Therefore, prevention of an age-graded decline in quadriceps muscle strength and peak V.O2 may need to become an outcome of pulmonary rehabilitation of patients with COPD

Effects of neuromuscular electrical stimulation of muscles of ambulation in patients with chronic heart failure or COPD: a systematic review of the English-language literature.

Despite optimal drug treatment, many patients with CHF or COPD still suffer from disabling dyspnea, fatigue and exercise intolerance. They also exhibit significant changes in body composition. Attempts to rehabilitate these patients are often futile because conventional exercise training modalities are limited by the severity of exertional dyspnea. Therefore, there is substantial interest in new training modalities that do not evoke dyspnea, such as transcutaneous neuromuscular electrical stimulation (NMES). Herein, we systematically review the literature that addresses the effects of NMES applied to the muscles of ambulation. We focused on the effects of NMES on strength, exercise capacity, and disease-specific health status in patients with CHF or COPD. We also address the methodological quality of the reported studies as well as the safety of NMES. Manuscripts published prior to December 2007 were identified by searching the Medline /PubMed, Embase, Cochrane Controlled Trials Register, CINAHL and The Physical Therapy Evidence Database (PEDro) databases. Fourteen trials were identified: nine trials that examined NMES in CHF and five in COPD. PEDro scores for methodological quality of the trials were generally moderate tot good. Many of the studies reported significant improvements in muscle strength, exercise capacity and/or health status. Nonetheless the limited number of studies, the disparity in patient populations and variability in NMES methodology prohibit the use of meta-analysis. Yet, from the viewpoint of a systematic review NMES looks promising as a means of rehabilitating patients with COPD and CHF. At least, there is sufficient evidence to warrant more large prospective RCTs

Characteristics and determinants of endurance cycle ergometry and six-minute walk distance in patients with COPD

Background: Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD). We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients.Methods: A dataset of 2053 COPD patients (43% female, age: 66.9 ± 9.5 years, FEV1% predicted: 48.2 ± 23.2) was analyzed retrospectively. Patients underwent, amongst others, respiratory function evaluation; medical tests and questionnaires, one maximal incremental cycle test where peak work rate was determined and two functional exercise tests: a CET at 75% of peak work rate and 6MWT. A stepwise multiple linear regression was used to assess determinants.Results: On average, patients had impaired exercise tolerance (peak work rate: 56 ± 27% predicted, 6MWT: 69 ± 17% predicted). A total of 2002 patients had CET time of duration (CET-Tend) less than 20 min while only 51 (2.5%) of the patients achieved 20 min of CET-Tend . In former patients, the percent of predicted peak work rate achieved differed significantly between men (48 ± 21% predicted) and women (67 ± 31% predicted). In contrast, CET-Tend was longer in men (286 ± 174 s vs 250 ± 153 s, p &amp;lt; 0.001). Also, six minute walking distance (6MWD) was higher in men compared to women, both in absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m, 72%predicted, p &amp;lt; 0.05). Gender was associated with the CET-Tend but BMI, FEV1 and FRC were related to the 6MWD highlighting the different determinants of exercise performance between CET and 6MWT.Conclusions: CET-Tend is a valuable outcome of CET as it is related to multiple clinical aspects of disease severity in COPD. Gender difference should temper the interpretation of CET. © 2014 Andrianopoulos et al.; licensee BioMed Central Ltd

Treatable Traits in the European U-BIOPRED Adult Asthma Cohorts

Letter to the edito